Reducing the scope for prevention of pneumococcal disease in older adults?

Pneumococcal pneumonia

Pneumococcal infection is the commonest cause of community acquired pneumonia, and there are effective vaccines to protect against it. It can also cause septicaemia and meningitis, and can result in death. Pneumococcal meningitis is as deadly as meningococcal meningitis, and there are up to 10 times as many deaths from pneumococcal disease as there are from meningococcal disease.  By far the highest number of hospitalisations and deaths for pneumococcal infections in Australia occurs in people aged >65 years. The causative bacteria, streptococcus pneumoniae, has over 90 different serotypes and vaccines must cover the most common serotypes that cause illness in humans. There are two types of pneumococcal vaccine available, the polysaccharide and conjugate types, with varying coverage of serotypes depending on the vaccine.

 

The incidence of invasive pneumococcal disease is highest at the extremes of age – in infants and older adults. The problem is, these same groups don’t have a robust immune system. Infants have a developing immune system and rely on maternal antibodies for the first six months of life while the thymus, an important immune organ, is still developing. Each vaccine dose in the infant immunisation schedule is given against a progressively strengthening immune system, which is a winning game with high rewards. In contrast, older adults face progressive decline of the immune system, a phenomenon called “immunosenescence” which occurs predictably in adults after the age of about 50 years. This decline in immune function is exponential, which means the risk of infection increases with age while the ability to respond robustly to vaccines declines, making older adults doubly disadvantaged. 

 

In 2005 Australia simultaneously introduced an infant vaccination program with the 7-valent conjugate pneumococcal vaccine, designed specifically to improve immune response in infants, and a program for every adult aged 65 years and over with the older polysaccharide vaccine. There has been a decline in pneumococcal infections since, even in people not in the infant or older adult groups, reflecting herd immunity. However, the exact contribution of the elderly and infant vaccination schedules in Australia to the burden of disease in adults has not been estimated well. It is clear the introduction of infant conjugate vaccination has resulted in herd immunity to other age groups, however there is accepted evidence of efficacy against invasive pneumococcal disease in adults over 65 years, and also evidence of prevention of community acquired pneumonia. An Australian study showed 65% effectiveness of the polysaccharide vaccine in adults >65 years. Research on vaccination of frail older people which we have done shows good immune responses to both pneumococcal vaccines, even in frail people with low immunity, with persistence of immunity for many serotypes. There is possibly also a benefit in giving a sequential schedule of the conjugate followed by the polysaccharide vaccines. Our recent study shows waning of functional immunity in older adults after 5 years, which raises the question about whether booster doses should be reinstated. 

 

A series of changes to the elderly vaccination program have occurred, including removal of the recommendation for the 5 yearly booster vaccine for all older adults. Currently, there is a proposal to review the cost-effectiveness of pneumococcal vaccines for adults and a change in recommendations for older adults is being considered. There is no clear justification provided for this, nor for focusing on only pneumococcal vaccination in older adults if cost-effectiveness is the only consideration. There are more costly vaccines given to prevent less common infections in infants (which is rightly a high priority), and from an equity perspective, principles of cost-effectiveness should not be applied selectively to only vaccines for older people.  Ageism in health care is a recognised problem, with lower value placed on disease prevention in older people, despite an ageing population. Facing an ageing population, vaccination is low hanging fruit for prevention of disease and the burden that places on the health care system. Acute care consumes over 90% of the health budget, and the majority of acute care in Australia is provided to older people. In 2018, people over 65 years accounted for 42% of all hospitalisations, a figure that is rising over time. Surely, then, prevention of disease in older people makes sense not only from a burden of disease perspective but also from an economic perspective. No cost-effectiveness analysis yet has considered the following factors:

 

  1. The WHO and Australia recognise antimicrobial resistance (AMR) as a serious problem. With rising AMR, including in community acquired pneumonia, primary prevention by vaccination is far better than trying to treat resistant infections. For many AMR infections, we have no vaccines. For pneumococcal disease, we do have effective vaccines. Consideration of the direct cost of AMR infections that are preventable by vaccines is essential if we are serious about AMR prevention strategies.

 

  1. There is a complex relationship between influenza and pneumococcal disease, with each infection predisposing to the other. Streptococcus pneumonia is the leading cause of secondary bacterial pneumonia following influenza infection. Therefore pneumococcal vaccination may also prevent complications of influenza, a cause of high morbidity and mortality every year.

 

  1. There is a growing body of evidence that infections can precipitate acute cardiovascular events and that vaccines (including pneumococcal vaccine) can prevent these events. Cardiovascular disease is the leading cause of death and illness worldwide, so any reduction by vaccination will be highly influential in public health impact and in estimates of cost-effectiveness.

 

  1. Bacterial pneumonia is a major cause of morbidity and mortality during influenza pandemics – including in 2009, yet pandemic planning generally fails to comprehensively address pneumococcal vaccination.

 

Finally, there is also an argument that cost-effectiveness analyses are not the best approach to evaluating vaccine programs. Given Australia started the funded infant and adult vaccination programs simultaneously, more nuanced analysis of the epidemiologic data are required to determine the separate impact of each vaccine program, rather than dismissing adult vaccination and attributing all reduction of disease to herd immunity from the infant program. Other available evidence needs to be considered in making policy changes, including clinical and immunological data, and evidence of direct health impacts such as prevention of AMR infections, cardiovascular disease and influenza-associated complications. Other high-income countries recommend pneumococcal vaccination for the elderly at age 65 years and above, as well as at-risk groups, because the evidence supports it, including the overwhelming preventable burden of disease in older adults. It would also be informative to model the excess burden of illness and deaths that would result from reducing the scope of prevention in the group with the highest risk of pneumococcal disease, the elderly.

 

By Raina MacIntyre